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Biomedical subjects

D Forsyth

Publications and source records attributed to D Forsyth.

14 recordsLinked to original sources
PubMed2005

Development and validation of a headspace method for determination of furan in food.

In the past furan had been found to form in foods during thermal processing. These findings and a recent classification of furan as a possible human carcinogen prompted us to develop a simple isotope dilution method for its determination in foods. We also investigated effects of furan volatility, sample matrix and partitioning of furan between water and fat constituents of sample on the analytical determination of furan. The method is based on headspace sampling of a 2 ml vial containing 1 g of sample. For analysis, samples were spiked with d(4)-furan, homogenized in a blender at 0 degree C, with water if required, and sub-sampled to vials containing sodium sulphate. After equilibration at 30 degrees C, 50 microl of headspace was injected into the split/splitless injection port of a GC/MS (EI, SIM). The method is linear in the 0.4-1000 ng/g range with a limit of detection of 0.1 ng/g.

Carcinogens↗
PubMed2004

Oral (gavage), in utero and postnatal exposure of Sprague-Dawley rats to low doses of tributyltin chloride. Part 1: Toxicology, histopathology and clinical chemistry.

Tributyltin (TBT) is a biocide that contaminates foods, especially shellfish. TBT is an endocrine disrupter in several marine species and is neurotoxic and immunotoxic in mammals. We have examined the effects of exposure to low doses of tributyltin chloride (TBTC) from day 8 of gestation until adulthood. Pregnant rats were gavaged daily with 0, 0.025, 0.25 or 2.5 mg TBTC/kg body weight from day 8 of gestation until weaning. Stomach contents of suckling pups contained undetectable levels of TBT and dibutyltin (DBT) levels were detectable only in the highest TBTC dose used, indicating negligible lactational transfer to pups. Post weaning, pups were gavaged daily with the same dose of TBTC administered to their mothers and sacrificed on post-natal days (PND) 30 (males and females), 60 (females) and 90 (males). TBTC had no effects on dams' body weights, food consumption, litter size, sex ratio or survival of pups to weaning. However, all doses of TBTC significantly affected parameters of the growth profile of the pups (mean body weights, average slope, curvature) and the ratio of weekly food consumption to weekly body weight gain indicated enhanced food conversion to body mass in females but a decreased conversion in males. Liver, spleen and thymus weights were also affected by TBTC. In male pups dosed at 2.5 mg/kg/day, reduced serum thyroxine levels were evident, indicating that the thyroid is a target for TBTC toxicity. No histopathological lesions were seen in the liver but elevated serum alanine aminotransferase, gamma-glutamyl transferase and amylase indicated hepatotoxicity. Significant decreases in liver weights in female pups exposed to 0.025 mg/kg/day TBTC were observed at PND 60. Decreases in spleen and thymus weights also pointed towards toxic effects of TBTC on the immune system. The 0.025 mg/kg/day TBTC should have been a no affect dose and yet this dose caused significant effects on growth profiles, decreased liver weights and elevated serum GGT levels in females.

Administration, Oral↗
PubMed2004

Developing quality indicators for older adults: transfer from the USA to the UK is feasible.

BACKGROUND: Measurement of the quality of health care is essential for quality improvement, and patients are an underused source of data about quality of care. We describe the adaptation of a set of USA quality indicators for use in patient interview surveys in England, to measure the extent to which older patients receive a broad range of effective health care interventions in both primary and secondary care. METHOD: One hundred and nineteen quality indicators covering 16 clinical areas, based on a set of indicators for the care of vulnerable elderly patients in the USA, were reviewed by a panel of 10 clinical experts in England. A modified version of the RAND/UCLA appropriateness method was used and panel members were supplied with literature reviews summarising the evidence base for each quality indicator. The indicators were sent for comment before the panel meeting to UK charitable organisations for older people. RESULTS: The panel rated 102 of the 119 indicators (86%) as valid for use in England; 17 (14%) were rejected as invalid. All 58 indicators about treatment or continuity and follow up were rated as valid compared with just over half (13 of 24) of the indicators about screening. CONCLUSIONS: These 102 indicators are suitable for use in patient interview surveys, including the English Longitudinal Study of Ageing (ELSA). The systematic measurement of quality of care at the population level and identification of gaps in quality is essential for quality improvement. There is potential for transfer of quality indicators between countries, at least for the health care of older people.

Aged↗
PubMed2000

The role of entacapone in the management of Parkinson's disease.

Catechol-O-methyltransferase (COMT) inhibition is an important advance in the treatment of Parkinson's disease. This consensus statement provides guidelines for the optimal use of the only currently available COMT inhibitor, entacapone (Comtess, Orion Pharma (UK) Ltd, Newbury, Berkshire).

Antiparkinson Agents↗
PubMed1994

Knowledge-based cephalometric analysis: a comparison with clinicians using interactive computer methods.

In modern orthodontic practice great reliance is placed on systematic and objective methods of characterizing craniofacial forms, using measurements based on both hard and soft tissue landmarks. Lateral skull X-ray images are routinely used in cephalometric analysis to provide quantitative measurements useful to clinical orthodontists. It is argued that a model- and knowledge-based methodology provides the best approach in successfully interpreting digitized lateral skull radiographs. A rule-based segmentation system, making use of an image appearance model, is used to extract image features from gray-level images. Complex image features and cephalometric landmarks are constructed from these segmented component features. A predictive model, defining picture structure, allows location hypotheses to be made for image features. The underlaying structure of the location model provides the basis for a geometric constraint model of use in discriminating between image feature candidates. A blackboard system is used to organize these tasks hierarchically, with individual knowledge sources grouped according to function and the individual stages of the adopted image interpretation cycle. Quantitative results demonstrate the superiority of this complex system over its component segmentation system run on its own. Comparisons with clinicians demonstrate both the strengths and the weaknesses of the present system. Comparisons with previous systems are favorable.

Cephalometry↗
PubMed1985

The effects on left ventricular performance of verapamil and metoprolol singly and together in exercise-induced angina pectoris.

Concurrent therapy with the calcium channel blocker, verapamil, and the beta-blocking group of compounds is usually felt to be clinically contraindicated due to the former's potent dromotropic and negative inotropic actions. The basis of this assumption was examined in a rest and exercise hemodynamic study of the effects of verapamil and the cardioselective beta-blocking drug, metoprolol, in 22 patients with stable angina pectoris and angiographically confirmed coronary artery disease. In a randomized study, 11 patients were assessed following intravenous verapamil (16 mg) alone, 11 following intravenous metoprolol (10 mg) alone, and all 22 were assessed on combination therapy. The plasma levels achieved at the time of each hemodynamic assessment were in the therapeutic range. At rest, verapamil alone significantly lowered systemic arterial pressure and vascular resistance; metoprolol alone lowered heart rate and increased systemic vascular resistance without change in systemic arterial pressure. Combination therapy reduced systemic arterial pressure and heart rate without change in cardiac output and systemic vascular resistance. During upright bicycle exercise, the changes were directionally similar. Depression of cardiac function (i.e., reduced cardiac output at increased pulmonary artery occluded pressure) occurred following metoprolol but not following verapamil; the addition of verapamil did not accentuate the depression of function induced by metoprolol. These results suggested that in patients with stable coronary artery disease, without manifest conduction system abnormality, the cardiac depressant actions of verapamil were countered by its vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

The effect on left ventricular performance of nifedipine and metoprolol singly and together in exercise-induced angina pectoris.

Clinical concern still exists regarding the potentially deleterious results of the combined negative inotropic effects of cardiac beta-adrenoceptor and slow calcium channel blockade in patients with impaired left ventricular function due to coronary heart disease. The haemodynamic effects of sublingual nifedipine (20 mg) and intravenous metoprolol (10 mg) singly and in combination were therefore studied in 20 patients with severe angina pectoris associated with angiographically documented coronary artery disease. The plasma concentrations of each drug at the time of the haemodynamic measurements were within the range associated with relief of exercise-induced anginal pain. Sitting at rest, nifedipine was associated with reductions in systemic arterial pressure (P less than 0.05), systemic vascular resistance (P less than 0.001), and increases in heart rate (P less than 0.01) and cardiac output (P less than 0.05) without significant change in the left heart filling pressure. In contrast, sitting at rest, metoprolol was associated with reductions in systemic blood pressure (P less than 0.05), heart rate (P less than 0.001) and cardiac output (P less than 0.05) and an increase in left heart filling pressure (P less than 0.01). After both drugs, similar directional changes were observed during upright bicycle exercise compared to the control exercise measurements. In combination, the negative inotropic effects of metoprolol were largely offset by the reduction of the systemic vascular resistance due to nifedipine. Conversely the reflex tachycardia following nifedipine was countered by metoprolol. Thus the combination reduced two of the major determinants of left ventricular oxygen consumption, namely heart rate and systemic blood pressure, at the expense of a small increase in left heart filling pressure. This may have explained the subjective improvement in anginal symptoms noticed by the majority of the patients. The combination of nifedipine and metoprolol was haemodynamically more advantageous both at rest and during exercise than either drug alone in our patients with depressed left ventricular function due to the coronary heart disease.

Adult↗
PubMedDate not supplied

A randomised study of the haemodynamic changes induced by venodilatation and arteriolar dilatation singly and together in left ventricular failure complicating acute myocardial infarction.

A randomised between-group study of the immediate haemodynamic effects of venodilatation by intravenous isosorbide dinitrate infusion (50-200 micrograms/kg/h) and arteriolar dilatation by intravenous hydralazine bolus (0.15 mg/kg) given either in random sequence (Groups 1 and 2; n = 12) or simultaneously (Group 3; n = 6) was undertaken in 18 men with radiographic and haemodynamic evidence (left ventricular [LV] filling pressure greater than 20 mm Hg) of LV failure 6-19 h following acute myocardial infarction. Control measurements (1 h) preceded either two consecutive 90-min treatment periods (Groups 1 and 2) or a single 90-min period (Group 3). Given independently, both drugs reduced systemic arterial pressure and vascular resistance, whereas only isosorbide dinitrate reduced LV filling pressure and only hydralazine increased cardiac output and stroke volume. Isosorbide dinitrate/hydralazine in combination significantly reduced LV filling pressure, systolic and diastolic arterial pressure, and total systemic vascular resistance. Cardiac output, stroke volume, and heart rate were increased. In conclusion, combined arteriolar dilatation and venodilatation appears to be of greater haemodynamic benefit than either alone, if the fall in mean systemic pressure does not compromise peripheral perfusion.

Adult↗
PubMedDate not supplied

Haemodynamic effects of selective alpha 1-blockade (trimazosin) in essential hypertension.

As a preliminary to a larger clinical trial, the haemodynamic effects of the selective alpha 1-adrenoceptor antagonist trimazosin were studied at rest and during bicycle exercise in the upright position in 14 patients with uncomplicated, stable essential hypertension. Rest and exercise studies before the drug was given revealed no evidence of left ventricular pumping deficiency. A single intravenous bolus of trimazosin (2 mg/kg) resulted in a plasma concentration of 13.1 +/- 1.0 mg/ml 30 min after injection. This plasma concentration of trimazosin was associated with a reduction in the systemic vascular resistance (p less than 0.01); in the absence of any increase in the cardiac output, this resulted in a fall in the systemic blood pressure (p less than 0.01) at rest. Heart rate and left heart filling pressure were unchanged. During 4 min of upright dynamic exercise after drug, the increment in systemic blood pressure was similar to that in the control study; i.e., the absolute level of pressure was reduced (p less than 0.01). The increases in heart rate, cardiac output, and left heart filling pressure during exercise were also unchanged after drug compared with those measured in the control study. The left heart filling pressure and cardiac output were slower to increase at the onset of exercise after trimazosin, which may imply a degree of venodilatation. There were no hypotensive symptoms or large falls in blood pressure after trimazosin at rest, but following 4 min of submaximal upright bicycle exercise, three of the 14 patients developed postural hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗